12-21370586-T-C

Variant names:

• chr12-21370586-T-C
• rs12826226
• ENST00000307378.10:c.-63+3813A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000307378.10(SLCO1A2):​c.-63+3813A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 150,654 control chromosomes in the GnomAD database, including 2,205 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.17 (2205 hom., cov: 29)
• Consequence: SLCO1A2 ENST00000307378.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28
• Publications: 4 publications found

Genes affected

SLCO1A2 (HGNC:10956): (solute carrier organic anion transporter family member 1A2) This gene encodes a sodium-independent transporter which mediates cellular uptake of organic ions in the liver. Its substrates include bile acids, bromosulphophthalein, and some steroidal compounds. The protein is a member of the SLC21A family of solute carriers. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Dec 2008]

IAPP (HGNC:5329): (islet amyloid polypeptide) This gene encodes a member of the calcitonin family of peptide hormones. This hormone is released from pancreatic beta cells following food intake to regulate blood glucose levels and act as a satiation signal. Human patients with type 1 and advanced type 2 diabetes exhibit reduced levels of the encoded hormone in blood and pancreas. This protein also exhibits a bactericidal, antimicrobial activity. [provided by RefSeq, Jul 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLCO1A2	NM_001386878.1	c.-63+32833A>G		intron_variant	Intron 1 of 14		NP_001373807.1
SLCO1A2	NM_001386881.1	c.-57-35882A>G		intron_variant	Intron 3 of 16		NP_001373810.1
SLCO1A2	NM_134431.5	c.-63+3813A>G		intron_variant	Intron 2 of 15		NP_602307.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLCO1A2	ENST00000307378.10	c.-63+3813A>G		intron_variant	Intron 2 of 15	1		ENSP00000305974.6
SLCO1A2	ENST00000453443.5	c.-63+32833A>G		intron_variant	Intron 1 of 4	3		ENSP00000409314.1
SLCO1A2	ENST00000450590.5	c.-58+32833A>G		intron_variant	Intron 1 of 3	4		ENSP00000407462.1

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25423 AN: 150538 Hom.: 2198 Cov.: 29

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.0608

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.180

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.169 AC: 25444 AN: 150654 Hom.: 2205 Cov.: 29 AF XY: 0.165 AC XY: 12143 AN XY: 73480

African (AFR) AF: 0.171 AC: 7009 AN: 41038

American (AMR) AF: 0.134 AC: 2021 AN: 15048

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 755 AN: 3450

East Asian (EAS) AF: 0.0611 AC: 310 AN: 5072

South Asian (SAS) AF: 0.148 AC: 700 AN: 4726

European-Finnish (FIN) AF: 0.145 AC: 1485 AN: 10264

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.183 AC: 12428 AN: 67756

Other (OTH) AF: 0.177 AC: 372 AN: 2100

Alfa AF: 0.177 Hom.: 1128

Bravo AF: 0.167

Asia WGS AF: 0.0990 AC: 345 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	11
DANN	Benign	0.76
PhyloP100		1.3
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12826226; hg19: chr12-21523520;